This proposal is aimed at two principal questions: Is it possible to manipulate the developmental fate of skeletal connective tissues by the application of tensile or compressive forces? And, how does Wolff's law manifest itself at the molecular level? We hope to approach these questions by the application, to isolated tissues maintained by sterile organ culture techniques, of a newly developed experimental system which was designed and built at the University of Vermont. Our system, based on a sterilizable feedback-controlled pneumatic forcing frame, has numerous technical advantages over previous experimental devices for the application of controlled stress to growing embryonic bones. The principal advantages are direct feedback control of the applied stress level, modularity of construction which allows rapid modification to suit a variety of tissue systems, a continuous direct measurement of the applied stress, and the simple incorporation of programming devices to achieve cyclic variation in the applied stress level. Preliminary experiments with a single pilot experimental unit demonstrate that it is well adapted for this project. A initial period of the proposed project will be devoted to the fabrication of additional experimental units, after which we will begin a systematic evaluation of the responses of embryonic or neonatal bone in organ culture to stress-mechanical stimulation. The continuing focus of the project will be on the interplay between applied stress and bone architecture. Analytical techniques will include gross measurement, polarized light microscopy in combination with histomorphometric analysis, histochemical analysis, and micromechanical testing.